Systematic review and meta-analysis of surgical drain management after the diagnosis of postoperative pancreatic fistula after pancreaticoduodenectomy: draining-tract-targeted works better than standard management

Drains' role after pancreaticoduodenectomy (PD) is debated by proponents of no drain, draining selected cases, and early drain removal. The aim of the study was to assess the effect of "standard" and "draining-tract-targeted" management of abdominal drains still in situ after diagnosing a postoperative pancreatic fistula (POPF)

Using the Process Digital Twin as a tool for companies to evaluate the Return on Investment of manufacturing automation

The fourth industrial revolution is gaining momentum, but still lacks full realization. Several studies suggest that many companies around the world have begun the digital transformation undertaking, but most are still far from full adoption and yet fail to see the full economic potential, being stuck in what has been called "pilot purgatory”. Digitalization is largely recognized as an accelerator and enabler for full automation in manufacturing, but companies are still struggling to assess the return on investment and the impact on operational performance indicators. Therefore, companies, especially SMEs characterized by dynamic, high-value, high-mix, and low-volume contexts, are reluctant to invest further. By incorporating simulation, data analytics and behavioral models, digital twins may also be used to support automation solutions ramp-up, demonstrate their impact evaluation, usage scenarios, eliminating the need for physical prototypes, reducing development time, and improving quality. Few forward-thinking companies are pursuing the digital transformation path, while the majority are clipping the wings of a transformation that is essential for a sustainable manufacturing. This paper describes a theoretical approach to exploit the digital twin technology to gather insights towards a realistic economical assessment of full automation solutions, to back and encourage investments to realize the potential of the digital manufacturing transformation. The approach is being tested under the European Union’s Horizon 2020 research and innovation program under grant agreement No. 958363, which provides an opportunity to assess how the various components of the method are constructed, how complex they are, and what level of effort is required, using a practical example

Duodenal Leiomyosarcoma Mimicking a Pancreatic Pseudocyst

A case of duodenal leiomyosarcoma presenting as a cystic mass is reported. Amylase, tumour markers levels in the cyst fluid and radiological findings suggested an inflammatory pancreatic pseudocyst. Exploratory laparotomy and frozen section examination showed a smooth muscle tumour of the duodenum. Pancreatoduodenectomy with pylorus-preser vation was performed and the patient remained symptom-free at 8 months follow-up

Comportamento de cópula de Spodoptera eridania (Walker) (Lepidoptera: Noctuidae).

Pouco se conhece sobre o comportamento de cópula de Spodoptera eridania (Walker) (Lepidoptera: Noctuidae), praga que tem ganhado importância nos últimos anos em vários cultivos agrícolas. Para tanto, foram estudados 61 casais virgens, durante oito noites após a emergência, em intervalos de 15 min, durante 14 horas. Os casais foram transferidos para tubo de PVC transparente e alimentados com solução de mel a 10%. Foi determinado a idade da primeira cópula, o número de cópulas por casal, o número de espermatóforos transferidos para cada fêmea e o horário de cópula. Os adultos copularam desde a primeira até a sétima noite após a emergência. Na primeira noite mais de 76% dos casais realizaram a primeira cópula, e até a quarta noite mais de 95% do total de cópulas foi observado. A partir da quarta noite, além da redução no número de cópulas, 50% das mesmas que ocorreram neste período tiveram duração inferior a 15 min, não caracterizando uma cópula duradoura onde pudesse haver a transferência de espermatóforos. Quando foram correlacionados o número de cópulas por casal com o número de espermatóforos transferido para a fêmea (correlação de 0,77), notou-se que nos casais onde houve estas cópulas rápidas, o número de espermatóros foi menor que o número de cópulas, sugerindo que não houve a transferência de espermatóforos, caracterizando este comportamento como tentativa de cópula e não como cópula efetiva. Outro aspecto observado no comportamento de S. eridania foi que 56% dos casais realizaram apenas uma cópula ao longo dos oito dias de avaliação, evidenciando uma tendência a "monoandria". O horário das cópulas foi predominantemente na oitava e nona hora da escotofase, se estendendo até a 11ª hora

Simple Detection of Large InDeLS by DHPLC: The ACE Gene as a Model

Insertion-deletion polymorphism (InDeL) is the second most frequent type of genetic variation in the human genome. For the detection of large InDeLs, researchers usually resort to either PCR gel analysis or RFLP, but these are time consuming and dependent on human interpretation. Therefore, a more efficient method for genotyping this kind of genetic variation is needed. In this report, we describe a method that can detect large InDeLs by DHPLC (denaturating high-performance liquid chromatography) using the angiotensin-converting enzyme (ACE) gene I/D polymorphism as a model. The InDeL targeted in this study is characterized by a 288 bp Alu element insertion (I). We used DHPLC at nondenaturating conditions to analyze the PCR product with a flow through the chromatographic column under two different gradients based on the differences between D and I sequences. The analysis described is quick and easy, making this technique a suitable and efficient means for DHPLC users to screen InDeLs in genetic epidemiological studies

Genome-scaled phylogeny of Saccharomyces cerevisiae from spontaneous must fermentations

Modern winemakers commonly inoculate selected S. cerevisiae strains in must to obtain controlled fermentations and reproducible products. However, wine has been produced for thousands of years using spontaneous fermentations from wild strains, a practice that is experiencing a revival among small wine producers. Despite the widespread usage of such strains in the past, there is much to know about their ecology, evolution and functional potential. For example, the reciprocal affinities of these strains within the S. cerevisiae phylogeny have yet to be discovered, as well as the degree of their biodiversity and their impact on wine terroir. To fill this knowledge gap, we aim at characterising at strain level the S. cerevisiae present in spontaneously fermented musts sampled across Italy. We set up a protocol based on polyphenols-removing prewashes, followed by whole-genome shotgun sequencing at a depth of 5Gb of DNA per sample. We performed both an assembly-free analysis to reconstruct the strain-level phylogeny of S. cerevisiae strains using the species-specific-marker based StrainPhlAn, and the reconstruction of Metagenome-Assembled Genomes of these strains for downstream functional analyses. To plan conservation acts in a scenario of continuous climate change, we aim at isolating and maintaining strains of interest. We will present preliminary results from the analysis of spontaneous musts sampled at different fermenting stages

A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma

Cancer therapy; Phase I trialsTeràpia del càncer; Assajos de fase ITerapia del cáncer; Ensayos de fase IBackground The first-in-class brain-penetrating synthetic hydroxylated lipid idroxioleic acid (2-OHOA; sodium 2-hydroxyoleate), activates sphingomyelin synthase expression and regulates membrane-lipid composition and mitochondrial energy production, inducing cancer cell autophagy. We report the findings of a multicentric first-in-human Phase 1/2A trial (NCT01792310) of 2-OHOA, identifying the maximum tolerated dose (MTD) and assessing safety and preliminary efficacy. Methods We performed an open-label, non-randomised trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumour activity of daily oral treatment with 2-OHOA monotherapy (BID/TID) in 54 patients with glioma and other advanced solid tumours. A dose-escalation phase using a standard 3 + 3 design was performed to determine safety and tolerability. This was followed by two expansion cohorts at the MTD to determine the recommended Phase-2 dose (RP2D). Results In total, 32 recurrent patients were enrolled in the dose-escalation phase (500–16,000 mg/daily). 2-OHOA was rapidly absorbed with dose-proportional exposure. Treatment was well-tolerated overall, with reversible grade 1–2 nausea, vomiting, and diarrhoea as the most common treatment-related adverse events (AEs). Four patients had gastrointestinal dose-limiting toxicities (DLTs) of nausea, vomiting, diarrhoea (three patients at 16,000 mg and one patient at 12,000 mg), establishing an RP2D at 12,000 mg/daily. Potential activity was seen in patients with recurrent high-grade gliomas (HGG). Of the 21 patients with HGG treated across the dose escalation and expansion, 5 (24%) had the clinical benefit (RANO CR, PR and SD >6 cycles) with one exceptional response lasting >2.5 years. Conclusions 2-OHOA demonstrated a good safety profile and encouraging activity in this difficult-to-treat malignant brain-tumour patient population, placing it as an ideal potential candidate for the treatment of glioma and other solid tumour malignancies. Clinical trial registration EudraCT registration number: 2012-001527-13; Clinicaltrials.gov registration number: NCT01792310.This study was supported in part by Laminar Pharmaceuticals. Financial support was also provided by the Govern de les Illes Balears i del Fons Social Europeu (ES01/TCAI/53_2016, ES01/TCAI/21_2017, ES01/TCAI/24_2018 and PROCOE/5/2017), the European Commission (H2020 Framework Programmes Project CLINGLIO 755179), Cancer Research UK (C9380/A25138) and the Experimental Cancer Medicine Centre Network (C9380/A25169). VL was supported by a Torres-Quevedo Research contract from the Spanish Ministerio de Economía y Competitividad (PTQ-17-09056), co-funded by the FSE